Roles of Iron Complexes in Catalytic Radical Alkene Cross-Coupling: A Computational and Mechanistic Study

A growing and useful
class of alkene coupling reactions involve
hydrogen atom transfer (HAT) from a metal-hydride species to an alkene
to form a free radical, which is responsible for subsequent bond formation.
Here, we use a combination of experimental and computational investigations
to map out the mechanistic details of iron-catalyzed reductive alkene
cross-coupling, an important representative of the HAT alkene reactions.
We are able to explain several observations that were previously mysterious.
First, the rate-limiting step in the catalytic cycle is the formation
of the reactive Fe–H intermediate, elucidating the importance
of the choice of reductant. Second, the success of the catalytic system
is attributable to the exceptionally weak (17 kcal/mol) Fe–H
bond, which performs irreversible HAT to alkenes in contrast to previous
studies on isolable hydride complexes where this addition was reversible.
Third, the organic radical intermediates can reversibly form organometallic
species, which helps to protect the free radicals from side reactions.
Fourth, the previously accepted quenching of the postcoupling radical
through stepwise electron transfer/proton transfer is not as favorable
as alternative mechanisms. We find that there are two feasible pathways.
One uses concerted proton-coupled electron transfer (PCET) from an
iron­(II) ethanol complex, which is facilitated because the O–H
bond dissociation free energy is lowered by 30 kcal/mol upon metal
binding. In an alternative pathway, an O-bound enolate-iron­(III)
complex undergoes proton shuttling from an iron-bound alcohol. These
kinetic, spectroscopic, and computational studies identify key organometallic
species and PCET steps that control selectivity and reactivity in
metal-catalyzed HAT alkene coupling, and create a firm basis for elucidation
of mechanisms in the growing class of HAT alkene cross-coupling reactions.